A Study of LY3434172, a PD-1 and PD-L1 Bispecific Antibody, in Advanced Cancer

NCT03936959 | Terminated Phase 1 Results FDA Drug

• 3 other identifiers: 17101J1E-MC-JZEA2018-003871-37
• Study Type: interventional
• Target: 10
• Locations: 5 countries
• Sites: 5

Brief Summary

The main purpose of this study is to evaluate the safety and tolerability of the study drug LY3434172, a PD-1/PD-L1 bispecific antibody, in participants with advanced solid tumors.

Conditions

Advanced Cancer

Keywords

PD-1; PD-L1

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Dose Limiting Toxicities (DLTs)

  A DLT is defined as adverse event/s of grade 3 or higher that occurs during the DLT observation period, which is Cycle 1 of each dose escalation cohort, and is clinically significant and definitely, probably, or possibly related to LY3434172, in the opinion of the investigator.

  Baseline through Cycle 1 (Up to 42 Day Cycle)

Secondary Outcomes (7)

• Pharmacokinetics (PK): Minimum Concentration (Cmin) of LY3434172

  PK: Cycle 1 Day 1 (C1D1): Predose; 1 hour(h); 3 h; 24 h; 72 h; 168 h post-infusion; Cycle 1 Day 15 (C1D15): Predose; 1 h; 3 h; 24 h; 72 h; 168 h post-infusion

• PK: Maximum Concentration (Cmax) of LY3434172

  PK: Cycle 1 Day 1 (C1D1): Predose; 1 hour(h); 3 h; 24 h; 72 h; 168 h post-infusion; C1D15: Predose; 1 h; 3 h; 24 h; 72 h; 168 h post-infusion

• PK: Area Under the Curve From Zero to Time to Last Measurable Concentration (AUC0-tlast) of LY3434172

  PK: Cycle 1 Day 1 (C1D1): Predose; 1 hour(h); 3 h; 24 h; 72 h; 168 h post-infusion; C1D15: Predose; 1 h; 3 h; 24 h; 72 h; 168 h post-infusion

• Objective Response Rate (ORR): Percentage of Participants With a Complete Response (CR) or Partial Response (PR)

  Baseline through Measured Progressive Disease (Up to 8.4 Months)

• Duration of Response (DOR)

  Date of CR or PR to Date of Objective Progression or Death Due to Any Cause (Up to 8.4 Months)

Study Arms (3)

3 Milligram (mg) - 10 mg LY3434172

EXPERIMENTAL

3 mg LY3434172 administered intravenously (IV) on Day 1 Cycle 1 of 28-day cycle. 10 mg LY3434172 administered IV on Day 15 Cycle 1 of 28-day cycle. Participants continued to receive study treatment until they met a criterion for discontinuation.

Drug: LY3434172

30 mg LY3434172

EXPERIMENTAL

30 mg LY3434172 administered IV on Day 1 and Day 15 of 28-day cycle. Participants continued to receive study treatment until they met a criterion for discontinuation.

Drug: LY3434172

100 mg LY3434172

EXPERIMENTAL

100 mg LY3434172 administered IV on Day 1 and Day 15 of 28-day cycle. Participants continued to receive study treatment until they met a criterion for discontinuation.

Drug: LY3434172

Interventions

LY3434172 DRUG

Administered IV

100 mg LY3434172; 3 Milligram (mg) - 10 mg LY3434172; 30 mg LY3434172

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Must have histological or cytological evidence of a diagnosis of cancer that is not amenable/resistant to approved standard-of-care therapy for the following solid tumors: Melanoma, non-small cell lung cancer (NSCLC), squamous cell carcinoma of the head and neck (SCCHN), urothelial cancer, gastric cancer, colorectal cancer, biliary tract cancer, anal cancer, nasopharyngeal cancer, esophageal cancer, SCLC, ovarian cancer, mesothelioma, pan-tumor MSIhi solid tumors, hepatocellular carcinoma, merkel cell cancer, cutaneous squamous cell carcinoma, endometrial cancer, breast cancer, cervical cancer, thyroid cancer, salivary cancer, and prostate cancer who have received at least one line of standard systemic therapy for their respective tumor type in the metastatic setting with progressive locally advanced or metastatic disease. Prior anti-programmed death 1 (PD-1) and anti-programmed death ligand 1 (PD-L1) allowed if they received another therapy immediately prior to this study or there has been a lapse of approximately ≥90 days from prior therapy.
• Must be willing to undergo pretreatment and on-treatment core needle or excisional tumor biopsies.
• Have at least one measurable lesion assessable as defined by the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
• Have adequate organ function.
• Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale.
• Have an estimated life expectancy of 12 weeks, in the judgment of the investigator.

You may not qualify if:

• Have symptomatic central nervous system (CNS) malignancy or metastasis not requiring concurrent treatment, including but not limited to surgery, radiation, corticosteroids and/or anticonvulsants to treat CNS metastases, and their disease is asymptomatic and radiographically stable for at least 30 days.
• Have moderate or severe cardiovascular disease.
• Have active or suspected autoimmune disease (eg. autoimmune vasculitis, autoimmune myocarditis, among others).
• Have serious concomitant systemic disorder that would compromise the participant's ability to adhere to the protocol, including known infection with human immunodeficiency virus (HIV) unless they are well controlled on highly active antiretroviral therapy (HAART) therapy with no evidence of acquired immune deficiency syndrome (AIDS)-defining opportunistic infections within the last 2 years, and CD4 T-cells count \> 350 cells/µl , active hepatitis B virus (HBV), active hepatitis C virus (HCV), active autoimmune disorders, or prior documented severe autoimmune or inflammatory disorders requiring immunosuppressive treatment.
• Use of escalating or chronic supraphysiologic doses of corticosteroids or immunosuppressive agents (such as, exceeding 10 milligrams/day of prednisone or equivalent). Use of topical, ophthalmic, inhaled, and intranasal corticosteroids permitted.
• Bowel obstruction, history or presence of inflammatory enteropathy or extensive intestinal resection, Crohn's disease, ulcerative colitis, or chronic diarrhea.
• Evidence of interstitial lung disease or noninfectious pneumonitis (active or treated by corticosteroid therapy).

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (5)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

St Vincent's Hospital

Sydney, New South Wales, 2010, Australia

Location

Universitair Ziekenhuis Gent

Ghent, 9000, Belgium

Location

Institut Claudius Regaud - IUCT Oncopole

Toulouse, 31059, France

Location

Asan Medical Center

Songpa-gu, Seoul, 05505, South Korea

Location

Related Links

• A Study of LY3434172, a PD-1 and PD-L1 Bispecific Antibody, in Advanced Cancer

Limitations and Caveats

Study terminated by sponsor.

Results Point of Contact

• Title: Chief Medical Officer
• Organization: Eli Lilly and Company

ClinicalTrials.gov@lilly.com

800-545-5979

Study Officials

• Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)

  Eli Lilly and Company

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 26, 2019
• First Posted: May 3, 2019
• Study Start: May 24, 2019
• Primary Completion: March 30, 2020
• Study Completion: April 29, 2021
• Last Updated: January 15, 2025
• Results First Posted: January 15, 2025

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1); US (1); AU (1); FR (1); BE (1)